Sitagliptin in Prevention of Type 2 Diabetes Mellitus (SITAGLIPTIN)

Does the DPP4 Inhibitor Sitagliptin Have a Role in Preventing Type 2 Diabetes- A Randomised Controlled Study.

The hypothesis is, in subjects with persistent impaired glucose tolerance(IGT) , sitagliptin will decrease the conversion rate to diabetes as compared to a placebo in three years.

Study Overview

• Status: Withdrawn
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: life style modification at base line; Drug: Sitagliptin

Detailed Description

The DPP-4 inhibitor Sitagliptin may be a suitable preventive agent in subjects with IGT or IFG on account of observed functional improvements in islet cell function and potential protective effect on beta cell mass.

Objectives of the study

1. Primary objectives :

   - To test whether the DPP4 inhibitor Sitagliptin is effective in preventing conversion of IGT to diabetes when compared with a placebo.

2. Secondary objectives:

   • To assess rates of reversal from IGT to Normal Glucose Tolerance (NGT) in IGT patients administered Sitagliptin
   • To assess the effect of Sitagliptin on measure of beta cell function and insulin resistance in patients with IGT.

Study design

Double blind placebo controlled, parallel group study - three years follow up .

Subjects with IGT in the age group of 30-55 years (n=900) will be identified by screening with a standard OGTT. Selected subjects will be randomized to the control arm using placebo and the two study arms using Sitagliptin. At baseline all group will receive a standard advice on lifestyle modification. The dose of sitagliptin will be 100 mg/d. The subjects will be reviewed at 6 monthly intervals and repeat OGTT will be done annually.

Proforma containing details of anthropometry, occupation, physical activity, diet habits, details of medications, regularity of treatment and biochemical investigations will be filled up at each interview.

Investigations:

Initial Screening

1. Demographic data
2. Height, weight, waist and hip measurements.
3. Details of family history of diabetes, hypertension and cardiovascular diseases.
4. History of any other major illness.
5. History of blood pressure and measurements.
6. Details of education and occupation.
7. Diet habits will be analyzed by dietician.
8. Details of physical activity will be assessed by a questionnaire.

Laboratory investigations:

1. Initial OGTT
2. Plasma glucose and HbA1c.
3. Lipid profile
4. Liver function tests
5. Serum amylase and serum lipase
6. Plasma insulin
7. 12 lead ECG.

Review analysis:

1. Review will be done with all clinical and biochemical assessment annually.
2. Evaluation of adherence to prescription will be done at 6 monthly intervals.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Tamil nadu
    • Chennai, Tamil nadu, India, 600 008
      • Dr.Ambady Ramachandran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects with IGT in the age group of 30-55 years (n=900) will be identified by screening with a standard OGTT.

Exclusion Criteria:

1. Known diabetes
2. Pregnant women
3. Alcohol abuse
4. Transferable jobs.
5. Subjects with major illness like cancer, hepatic or cardiac diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 1; Advice life style at baseline only	Other: life style modification at base line; Advice on physical activity, diet and drug adherence.
ACTIVE_COMPARATOR: sitagliptin arm : 2; 100mg/day sitagliptin advice on life style modification at baseline only	Drug: Sitagliptin; 100mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1. Rate of conversion of IGT to diabetes. 2. Relative reduction of incidence of diabetes by Sitagliptin among people with IGT compared to Placebo. 3. Increase in reversal of IGT to NGT	At intervals -6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
1. Beneficial effects in beta cell function. 2. Changes in insulin resistance 3. Improvement in cardiovascular risk factors by Sitagliptin.	Annual

Collaborators and Investigators

• Sponsor: India Diabetes Research Foundation & Dr. A. Ramachandran's Diabetes Hospitals

Publications and helpful links

General Publications

• 1.Ramachandran A, Ronald Ma, Snehalatha C. Diabetes in Asia. 2009 Lancet Oct;DOI:10.1016/S0140-6736(09)60937-5. 2.Snehalatha C, Mary S, Selvam S, Sathish Kumar CK, Shetty SB, Nanditha A, Ramachandran A. Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1).Diabetes Care. 2009 Oct;32(10):1796-801. 3.Ramachandran A, Snehalatha C, Mary S, Selvam S, Sathish Kumar CK, Catherin Seeli A, Samith Shetty A. Pioglitazone does not enhance effectiveness of life style modification in prevening conversion of impaired glucose tolerance to diabetes in Asian Indians-Results of Indian Diabetes Prevention Programme- (IDPP-2).Diabetologia 2009; 52: 1019 - 1026. 4.Ramachandran A, Snehalatha C. Cardiovascular risk factors in normoglycaemic Asian Indian population-Impact of urbanization. Diabetologia 2009 52; 596-599.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ANTICIPATED): February 1, 2014
• Study Completion (ANTICIPATED): December 1, 2014

Study Registration Dates

• First Submitted: December 22, 2009
• First Submitted That Met QC Criteria: December 23, 2009
• First Posted (ESTIMATE): December 24, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Sitagliptin; Prevention of type 2 diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: SITAGLIPTIN-003 IDRF